More than 40% of compounds identified by high-throughput screening are poorly water soluble. The low drug solubility leads to poor bioavailability. Nanosizing technique is an important approach to increase the drug solubility and dissolution rate, and further to imporve the drug biovalibility. Here, a fast wet milling was employed to prepare the nanosuspensions. 4 types of stabilizers (pluronic F68, pluronic F127, Tween 80 and PEG) at 4 different concentrations (10%, 25%, 60% and 80%, to drug amount) were performed on 2 structurally different drug substances: indomethacin and itraconazole. The effect of milling time, stabilizer type and concentration on particle size and size distribution were investigated. Photon correlation spectroscopy (PCS) results showed that nanosuspensions with the smallest size and polydisperisity index (PI) were obtained when 80 wt% F68 was used as the stabilizer for indomethacin and 60 wt% F127 for itraconazole. The morphology of nanoparticles was observed by transmission electron microscopy (TEM). The dissolution profiles of nanosuspensions and physical mixture suspensions were determined. Compared to the physical mixtures, dissolution rates of the nanosuspensions were significantly increased. The differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) were used to compare the crystalline state of the freeze-dried nanosuspensions before and after milling. The results indicated that the crystalline state of drugs were not changed by milling. The physical and chemical stability after 2 months storage at room temperature and at 4 °C were tested by PCS, TEM and high-performance liquid chromatography (HPLC). The nanosuspensions showed a good physical and chemical stability at both temperatures.
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